Homobenzylic ethers with pendent enol acetate nucleophiles undergo highly efficient cleavage reactions followed by 6-endo cyclizations to form 2,6-disubstituted tetrahydropyrones with excellent stereocontrol at room temperature in the presence of the mild oxidant ceric ammonium nitrate. Cyclizations proceed through either stabilized or nonstabilized oxocarbenium ions. Structure-reactivity relationships are presented to provide a predictive guide for the design of radical cation cleavage processes. Unique sequences for preparing cyclization substrates based on stereoselective Lewis acid mediated acetal openings have been developed for the synthesis of complex substrates that are suitable for applications to the synthesis of biologically active natural products.